It is becoming common for whole blood collected from a donor to be separated into—blood component preparations, such as an erythrocyte preparation, a thrombocyte preparation, and a blood plasma preparation, are separated from whole blood collected from a donor, stored and then provided for transfusion. Since microaggregates and leukocytes included in these blood preparations cause various side effects of blood transfusion, the number of occasions for removing these undesirable components before blood transfusion has been increasing. Particularly, in recent years, the need for leukocyte removal has widely been recognized. The number of countries legislating application of a process of removing leukocytes from all of blood preparations for blood transfusion and subsequent use thereof for transfusion has been increased.
As a method of removing leukocytes from blood preparations, processing blood preparations using a leukocyte removal filter is most typical. Processing the blood preparations using the leukocyte removal filter often performed at the bedside when a blood transfusion operation is performed. In recent years, however, in order to improve quality control of leukocyte-free preparations and the effectiveness of leukocyte removal process, it is more common, particularly in developed countries, to process the blood preparations in blood centers before storing the blood preparations (pre-storage leukocyte removal).
A blood collection-separation set typically consisting of two to four flexible bags, a tube connecting these bags, an anticoagulant, an erythrocyte preservation solution, a blood collection needle and the like has been used for collecting blood from a donor, separation into a plurality of blood components, and storing the blood components. A system in which a leukocyte removal filter is incorporated into such a blood collection-separation set has been widely used as a suitable system for use in the aforementioned “pre-storage leukocyte removal”, and is referred to as a “closed system”, an “integrated system” or the like. These systems are disclosed in Japanese Unexamined Patent Publication No. H1-320064, International Publication No. WO 92/020428 and the like.
Conventionally, a filter element made of nonwoven fabric or a porous body packed in a hard container of polycarbonate or the like has been widely used as a leukocyte removal filter. However, since the container has a low gas permeability, there is a problem that it is difficult to apply steam sterilization, which is widely used as a sterilization process for blood collection-separation sets. In one type of the closed system, leukocytes are first removed from the whole blood preparation after blood collection, the leukocyte removal filter is separated, and then a centrifugal operation for component separation is applied. In another case, first, a plurality of blood components are separated by centrifuging the whole blood, and subsequently the leukocytes are removed. In the latter case, the leukocyte removal filter is also centrifuged together with the blood collection-separation set. At such time, a hard container may damage bags and tubes, or the hard container itself may not withstand the stress and may break during centrifugation.
As a method for solving these problems, flexible leukocyte removal filters have been developed in which a material having excellent flexibility and steam permeability identical or similar to the material used for the bags of the blood collection-separation set is used for the container. These flexible leukocyte removal filters that adopt a container made of a material having excellent flexibility and steam permeability can be broadly classified into a type in which the filter element is once welded to a sheet-shaped flexible frame, and subsequently the filter is welded to a housing material (see Description of European Patent No. 0526678 and Japanese Unexamined Patent Publication No. H11-216179), and a type in which a flexible container is directly welded to the filter element (see Japanese Unexamined Patent Publication No. H7-267871 and International Publication No. WO 95/017236). Hereinafter, the former is sometimes referred to as a frame welding type and the latter is sometimes referred to as a container welding type.
Typically, in the case of processing blood with these types of leukocyte removal filters, a bag that contains a blood preparation to be processed and is connected to a blood inlet side of the filter via a tube is placed at a height that is approximately 20 to 100 cm above the filter to allow the blood preparation to pass through the filter by the action of gravity. The filtered blood preparation is stored in a recovery bag connected to a blood outlet side of the filter via a tube. During filtration, a pressure loss occurs due to the resistance of the filter element, whereby the pressure in a space on the inlet side of the filter becomes a positive pressure. In the case of the filter that includes a flexible container, there is a tendency for the flexibility of the container itself to cause the container to swell like a balloon due to the positive pressure, thereby pressing the filter element against the container on the outlet side.
Furthermore, typically, a bag for storing blood having been processed with the blood filter is placed at a position that is 50 to 100 cm lower than the filter. Since blood moves through a flow path on the downstream side due to the action of gravity, there is a tendency for the outlet side of the filter to become a negative pressure, and the flexible container is prone to be in close contact with the filter element.
That is, it has been pointed out previously that a filter adopting a flexible container has a problem in that there is a strong tendency for the filter element to be in close contact with the outlet-side container due to the dual force, and thus the flow of blood is impeded and an adequate flow rate cannot be obtained.
To address the problem, a blood processing filter including a flow path securing sheet disposed between a filter element and an outlet-side flexible container has been proposed (International Publication No. WO 2012/039400). The flow path securing sheet is provided with a plurality of slit-shaped flow path holes formed by cutting the sheet. Consequently, even if a dual force is applied during filtration, a blood flow path is secured between the flow path holes in the flow path securing sheet and the outlet port, and a sufficient flow rate can be obtained.